The objective of this study is to pursue further characterization of the disturbed neuroendocrine function of patients with depression, in particular hypothalamic-pituitary-adrenocortical (HPAC) function with special attention to ACTH, because of the implications of aspects of neuroendocrine function as a potential contributor to the development or persistence of depressive illness in selected individuals, as a biological marker of a subgroup of depressed patients, and as tool(s) for predicting response to specific forms of treatment. Important specific aspects of this objective are: 1) to ascertain the clinical characteristics of patients with disturbed HPAC function, 2) to examine patients with Cushing's syndrome, who have neuroendocrine abnormalities similar to patients with primary depression, as regards their clinical psychopathology and potential abnormalities in brain monoamine metabolism, 3) to examine the clinical and HPAC system response of depressed patients to a clinically used drug effective in the control of Cushing's syndrome (cyproheptadine), 4) to begin studies to elucidate why depressed patients with persistently increased HPAC function do not show the stigmata of Cushing's disease, 5) to test the hypothesis that severely depressed patients do not have only a state (depression) related abnormality of HPAC activity but that at least in some this is a trait that never returns to normal even after remission from clinical depression, 6) to relate pretreatment ACTH levels and ACTH secretory profile to psychopathology and response to treatment, 7) to examine the relationship between aspects of pretreatment dexamethasone suppression and subsequent response to antidepressant therapy, 8) to determine whether behavioral and HPAC response to a single dose of d-amphetamine is a predictor of differential response to amitriptyline vs. desipramine antidepressant treatment, and 9) to examine the relationship between ACTH pulsatile release and pulses of plasma cortisol in depressed patients.